Pharmacology PPT

1. PHARMACOVIGILANCE
EXERCISE
Dr. Chintan Doshi

2. LEARNING OBJECTIVES
• Should be able to fill the ADR form
• Should be able to do causality assessment

3. INTRODUCTION
Pharmacovigilance: The science and activities
related to
 detection
 assessment
understanding
prevention of adverse effect or any drug
related problem.

4. IMPORTANT DEFINITIONS
Adverse Event: Any untoward medical occurrence that
may present during treatment with a pharmaceutical
product but which does not necessarily have a causal
relationship
Adverse drug reaction: A response which is noxious and
unintended and which occurs at doses normally used in
humans for prophylaxis, diagnosis, or therapy of disease or
for the modification of physiological function.(WHO,1972).

5. IMPORTANT DEFINITIONS…
Side Effect: Any unintended effect of a
pharmaceutical product occurring at normal dosage
which is related to the pharmacological property of
the drug.
Unexpected Adverse reaction: An adverse reaction,
the nature or severity of which is not consistent with
domestic labeling or market authorization, or
expected from characteristic of the drug.

6. IMPORTANT DEFINITIONS…
 Rechallenge : time at which drug is again
given to the patient after it previous withdrawal
Negative
Positive
 Dechallenge: withdrawl of the drug from the
patient
Negative
Positive

7. How to fill the form?
• A 59 Year old male Raman Srivastav
complained of gradually increasing lethargy,
numbness and tingling sensations of hands
and feet for last 2 months.
• His son informed that there was a perceptible
change in mental processes since last one
month.
• He now avoids taking decisions and tries to
postpone important works.

8. • He was known case of diabetes melitus and
was taking gliclazide-160mg/day and
metformin 1.5 gm/day both in three divided
doses for last 5 years.
• His blood glucose remained around 130
mg(fasting) and 150 mg/dl (Post meals)
• He took regular diet and non vegetarian,
taking chicken twice a week.
• He did not take alcohol and was nonsmoker.
• His bowel habit was normal

9. • Neurological examination showed loss of
vibration and touch sensations in both feet.
• Other systemic examination was normal.
• Investigations revealed Hb1Ac -7.8%, SGPT-38,
SGOT- 32IU.
• Vibration testing by bioasthesiometer showed
moderate neuropathic pattern in both feet.
• Serum Vitamin B12 levels were 60
pg/ml(Normal>140pg/ml)

10. • Metformin was substituted by
voglibose(0.3mg twice a day) and injectable
methylcobalamine was started.
• He gradually improved in 3 weeks, with
marked reduction in numbness and tingling
and improvement of vibration threshold.
• The repeat serum B12 level was 455pg/ml

11. R.S. 59 Y
Gradually increasing
• Lethargy
• Numbness
• Tingling sensation on hand and feet- past 2 months
Perceptible change in mental process past one month
Patient avoid taking decision and tries to postpone
works
last 3 months

12. Metformin 500mgoral TDS 5 YEAR Diabetes Melitus
Tab. Gliclazide- 160 mg/day, orally in three
devided doses for last 5 years

13. Vitamn B12- 60 pg/ml, after 3 weeks of withdrawal of metformin VitB12 – 455 pg/ml
HbA1c – 7.8%
SGPT- 38 IU SGOT- 32 IU
Neurological Examination : Loss of vibration and touch sensation in both feet
•Known case of Diabetes mellitus
•Diet: Regular, Nonveg
•Non alcoholic/ Non smoker

14. Metformin 500mgoral TDS 5 YEAR Diabetes Melitus
Tab. Gliclazide- 160 mg/day, orally in three
devided doses for last 5 years
WHO- probable
Naranjo - Probable

15. • Certain
• Probable
• Possible
• Unlikely
• Conditional/Unclassified
• Unassessable/Unclassifiable
WHO-UMC
Causality Scale

16. WHO-UMC
Causality Scale
• Certain:
• Event or laboratory test abnormality, with
plausible time relationship to drug intake
• Cannot be explained by disease or other drugs
• Response to withdrawal plausible
(pharmacologically, pathologically)
• Rechallenge satisfactory, if necessary

17. PROBABLE
• Event or laboratory test abnormality, with
reasonable time relationship to drug intake
• Unlikely to be attributed to disease or other
drugs
• Response to withdrawal clinically reasonable
• Rechallenge not required

18. POSSIBLE
• Event or laboratory test abnormality, with
reasonable time relationship to drug intake
• Could also be explained by disease or other
drugs
• Information on drug withdrawal may be
lacking or unclear

19. UNLIKELY
• Event or laboratory test abnormality, with a
time to drug intake that makes a relationship
improbable (but not impossible)
• Disease or other drugs provide plausible
explanations

20. Categories Time
sequence
Other
drugs/disease
ruled out
Dechallenge Rechallange
Certain yes yes yes Yes
Probable Yes Yes Yes No
Possible Yes No NO No
Unlikely No No No No

21. In present case WHO scale
• Temporal relationship – yes/no
Yes
• Ruling out of other explanations:
Is the Diabetes responsible?
Diabetes seems unlikely to cause B12 deficiency
Pure sensory distal neuropathy is more common in
diabetes
Is it due to gliclazide or Metformin?
Gliclazide is not known to cause of vit B12 deficiency.

22. • Dechallange : Positive
• Rechallange : Not done
• PROBABLE

23. NARANJO CAUSALITY
ASSESSMENT SCALE

24. Questions Yes No Don’t
Know
1) Are there previous conclusive reports on this reaction? +1 0 0
2) Did the ADR appear after the suspected drug was
administered?
+2 -1 0
3) Did the ADR improve when the drug was discontinued? +1 0 0
4) Did the ADR appear with re-challenge? +2 -1 0
5) Are there alternative causes for the ADR? -1 +2 0
6) Did the reaction appear when placebo was given? -1 +1 0
7) Was the drug detected in blood at toxic levels? +1 0 0
8) Was the reaction more severe when the dose was
increased, or less severe when the dose was decreased?
+1 0 0
9) Did the patient have a similar reaction to the same or
similar drug in any previous exposure?
+1 0 0
10) Was the ADR confirmed by any objective evidence? +1 0 0

25. The Naranjo Probability Scale
The score :-
> 8 = Certain
5-8 = probable
1-4 = possible
0 = doubtful

26. Questions Yes No Don’t
Know
1) Are there previous conclusive reports on this reaction? +1 0 0
2) Did the ADR appear after the suspected drug was
administered?
+2 -1 0
3) Did the ADR improve when the drug was discontinued? +1 0 0
4) Did the ADR appear with re-challenge? +2 -1 0
5) Are there alternative causes for the ADR? -1 +2 0
6) Did the reaction appear when placebo was given? -1 +1 0
7) Was the drug detected in blood at toxic levels? +1 0 0
8) Was the reaction more severe when the dose was
increased, or less severe when the dose was decreased?
+1 0 0
9) Did the patient have a similar reaction to the same or
similar drug in any previous exposure?
+1 0 0
10) Was the ADR confirmed by any objective evidence? +1 0 0
CERTAIN PROBABLE
POSSIBLE DOUBTFUL

27. Preventability assessment
(Schumock and Thornton Scale)
1-Was the drug involved in the ADR not considered
appropriate for the patient's clinical condition?
2-Was the Dose, route or frequency of
administration inappropriate...?
3-Was required therapeutic drug monitoring or
other necessary laboratory test not performed?
4-Was there a history of allergy/previous reaction
to the drug?

28. • 5-Was a drug interaction involved in the ADR?
6-Was a toxic serum drug documented?
7-Was poor compliance involved in the
reaction?
• Result: If answer of any of 7 questions is
“YES” then ADR is preventable.

29. Case 2
• A 25 years old male patient was diagnosed as
a case of URTI for that he was given T.
Levofloxacin 500 mg Once in a Day.
• He developed pigmented lesion on the lateral
aspect of the left palm after 2 days , for that
he came to skin OPD G.G.Hospital , Jamnagar.
• It was diagnosed as Fix Drug Reaction .
• He was advised to stop T. Levofloxacin and
was switch over to T.Azithro.

30. Case 2
• Lesion gradually disappeared within 4 days.
• Patient had a past history of similar lesion at
the same site with the same drug but at that
time patient had ignored it.

31. WHO causality
• Proper timing,
• no other cause,
• Dechallange +ve
• Rechallange +ve ……. DEFINITE

32. Questions Yes No Don’t
Know
1) Are there previous conclusive reports on this reaction? +1 0 0
2) Did the ADR appear after the suspected drug was
administered?
+2 -1 0
3) Did the ADR improve when the drug was discontinued? +1 0 0
4) Did the ADR appear with re-challenge? +2 -1 0
5) Are there alternative causes for the ADR? -1 +2 0
6) Did the reaction appear when placebo was given? -1 +1 0
7) Was the drug detected in blood at toxic levels? +1 0 0
8) Was the reaction more severe when the dose was
increased, or less severe when the dose was decreased?
+1 0 0
9) Did the patient have a similar reaction to the same or
similar drug in any previous exposure?
+1 0 0
10) Was the ADR confirmed by any objective evidence? +1 0 0

33. Preventability assessment
(Schumock and Thornton Scale)
1-Was the drug involved in the ADR not considered
appropriate for the patient's clinical condition? -
NO
2-Was the Dose, route or frequency of
administration inappropriate...? - NO
3-Was required therapeutic drug monitoring or
other necessary laboratory test not performed?-
NO
4-Was there a history of allergy/previous reaction
to the drug? - YES

34. Preventability assessment
(Schumock and Thornton Scale)…
5-Was a drug interaction involved in the ADR?-
NO
6-Was a toxic serum drug documented?- NO
7-Was poor compliance involved in the
reaction?- NO
• Result: preventable.